Improved approach for normothermic machine perfusion of cold stored kidney grafts

Normothermic machine perfusion can decrease reperfusion injury in renal transplantation. Clinical procurement logistics include retrieval and initial transport of the graft using static cold storage. Therefore, use and benefits of brief normothermic reconditioning by machine perfusion should be investigated in the initially cold preserved graft. Porcine kidneys (6 per group) were retrieved 20 min after cardiac standstill. After 20 h of static cold preservation some grafts were put on a machine perfusion circuit and normothermically perfused for 2 h at 35°C (NMP). Another group was subjected to controlled oxygenated rewarming (COR), starting perfusion at 8°C and elevating temperature and pressure slowly up to 35°C and 75 mmHg during the first 90 min of 2 h perfusion. Control kidneys were only cold stored (CS). Post implant graft function was evaluated afterwards in an established in vitro reperfusion model. During graft reconditioning, COR reduced oxygen free radical production and formation of 4-hydroxy-2-nonenal (HNE), an activator of mitochondrial uncoupling proteins, in comparison to NMP. Upon reperfusion, NMP only led to a slight improvement of renal function (clearance of creatinine, fractional excretion of Na and glucose) compared to controls. But 2-3 fold improvements of renal function were seen after COR, which also significantly improved aerobic efficiency (total Na absorption/VO₂) upon reperfusion. A slow and controlled increase in temperature up to normothermia improves mitochondrial recovery and oxygen utilization efficiency, resulting in better functional recovery, possibly through a more mild and adapted increase of cellular metabolism.